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1.
JCEM Case Rep ; 2(2): luae017, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38405103

RESUMO

Doege-Potter syndrome occurs when incompletely processed insulin-like growth factor 2 (IGF-2), also known as big IGF-2, is produced by a solitary fibrous tumor (SFT) and results in non-islet cell tumor hypoglycemia (NICTH). We discuss here the case of a 66-year-old male who presented with a 2-week history of increasing confusion and a serum glucose of 34 mg/dL. The patient's symptoms immediately improved with dextrose. The patient did not use insulin, serum sulfonylurea screen was negative, and testing for adrenal insufficiency was unremarkable. Outpatient laboratory evaluation revealed a serum glucose of 48 mg/dL along with low insulin, C-peptide, and proinsulin levels. Further work-up showed an IGF-2 to IGF-1 ratio of 38:1. A ratio greater than 10:1 is diagnostic of NICTH. Imaging demonstrated a 21-cm mass in the lower abdomen and pelvis. The patient underwent surgical resection. The hypoglycemia resolved immediately postoperatively. Surgical pathology revealed a malignant SFT. In NICTH, big IGF-2 forms a complex that is biologically active and saturates the insulin and IGF receptors, resulting in refractory hypoglycemia. Although glucocorticoids can mitigate hypoglycemia, complete surgical resection is the only definitive treatment of NICTH. This case highlights the importance of maintaining a broad differential for seemingly simple hypoglycemia.

2.
Cureus ; 15(11): e48994, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38111444

RESUMO

BACKGROUND AND AIM: While proton pump inhibitor (PPI) therapy has proven to be effective in managing gastroesophageal reflux disease (GERD), a notable portion of patients who experience GERD symptoms may not respond to this treatment. Research suggests that roughly 30% of individuals with a presumed GERD diagnosis may continue to experience symptoms, whether partially or completely, even when receiving PPI therapy. The aim of this study was to assess the treatment of gastrointestinal diseases with a novel potassium-competitive acid blocker (P-CAB), vonoprazan, in terms of its effectiveness and safety in the Pakistani population. METHODS: This prospective, multicenter, observational study was conducted in Pakistan. This study included 1,642 patients from January 2023 to August 2023, aged 18 years, with gastrointestinal disorders. All demographic data, medical history, GERD severity assessment questionnaire (GerdQ), and laboratory parameters, including stool assessment for Helicobacter pylori (H. pylori), were observed. Patients were orally treated with vonoprazan at doses of 10 mg or 20 mg, once or twice daily. Statistical analysis was done by one-way ANOVA. RESULTS: Out of 1,642 patients, 840 (51.2%) were males and 802 (48.8%) were females, with a mean age of 39.81±14.61 years. The mean GerdQ score at baseline was 20.37±15.87, 7.24±8.15 at the second week of treatment, and 3.70±6.31 at the fourth week of treatment (p<0.001). 90.74% of patients achieved H. pylori eradication. Most patients were acid regurgitation and heartburn-free for >70% of days. Most of the patients, 1,283 (78.13%), exhibited good treatment compliance. Mild adverse events were reported in 37 (2.3%) patients. CONCLUSIONS: The use of vonoprazan significantly reduced the likelihood of GERD by improving symptoms and was also highly effective in the elimination of H. pylori infections. Vonoprazan was generally well tolerated.

3.
J Microencapsul ; 40(4): 217-232, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36752024

RESUMO

Azithromycin is an antibiotic proposed as a treatment for the coronavirus disease 2019 (COVID-19) due to its immunomodulatory activity. The aim of this study is to develop dry powder formulations of azithromycin-loaded poly(lactic-co-glycolic acid) (PLGA) nanocomposite microparticles for pulmonary delivery to improve the low bioavailability of azithromycin. Double emulsion method was used to produce nanoparticles, which were then spray dried to form nanocomposite microparticles. Encapsulation efficiency and drug loading were analysed, and formulations were characterised by particle size, zeta potential, morphology, crystallinity and in-vitro aerosol dispersion performance. The addition of chitosan changed the neutrally-charged azithromycin only formulation to positively-charged nanoparticles. However, the addition of chitosan also increased the particle size of the formulations. It was observed in the NGI® data that there was an improvement in dispersibility of the chitosan-related formulations. It was demonstrated in this study that all dry powder formulations were able to deliver azithromycin to the deep lung regions, which suggested the potential of using azithromycin via pulmonary drug delivery as an effective method to treat COVID-19.


Assuntos
COVID-19 , Quitosana , Nanopartículas , Humanos , Azitromicina , Pós , Administração por Inalação , Tratamento Farmacológico da COVID-19 , Aerossóis e Gotículas Respiratórios , Tamanho da Partícula
4.
Transplant Proc ; 55(1): 103-108, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36577635

RESUMO

BACKGROUND: Urinary tract infections (UTIs) are the most prevalent type of kidney transplant (KT) recipients. We aimed to investigate the incidence, causes, and clinical impact of early recurrent UTI post-living donor KT and to examine the role of behavioral education program in management. METHODS: This retrospective cohort chart-review study included all KT recipients with recurrent UTI necessitating hospital admission between September 2017 and August 2021. All patients with recurrent UTI were subjected to behavioral education for a month. RESULTS: UTI was found in 14 of 145 patients (9.6%), with recurrent UTI in 11 (7.6%). A total of 93% of UTIs occurred during the first 6 months post-transplant and represented 52% of KT readmissions during the same period. A total of 64.3% of patients were older than 50 years. The mean (SD) length of hospital stay was 5 (2.5) days, with an equal incidence in both sexes. The most common bacterial isolates in early recurrent UTI were Escherichia coli in 80.9%. Both Extended-spectrum beta-lactamases and multidrug-resistant organisms (resistance in ≥3 drugs) were seen in 82.4% of isolates. Furthermore, the most effective antibiotic was meropenem, with 86.7% effectiveness. A total of 65% of UTIs were managed with a single antibacterial course. A total of 64.3% of patients were older than 50 years. In patients who developed UTI, the mean (SD) serum creatinine was 1.31 (0.52) mg/dL, with a mean increase in serum creatinine of 0.19 mg/dL on having the episodes; at 1 year post-transplant, serum creatinine declined to 1.23 (0.43) mg/dL. Four patients (36%) had no recurrence of UTI after behavioral education. CONCLUSIONS: The multidrug-resistant bacterial isolates account for 82.4% of the UTIs. Therefore, antibiotic prescription should follow the antimicrobial stewardship guidelines. Behavioral education significantly reduced the incidence of recurrent UTI.


Assuntos
Transplante de Rim , Infecções Urinárias , Masculino , Feminino , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Creatinina , Doadores Vivos , Antibacterianos/uso terapêutico , Escherichia coli , Infecções Urinárias/etiologia , Transplantados
6.
Expert Syst Appl ; 200: 116834, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36034050

RESUMO

Classification accuracy achieved by a machine learning technique depends on the feature set used in the learning process. However, it is often found that all the features extracted by some means for a particular task do not contribute to the classification process. Feature selection (FS) is an imperative and challenging pre-processing technique that helps to discard the unnecessary and irrelevant features while reducing the computational time and space requirement and increasing the classification accuracy. Generalized Normal Distribution Optimizer (GNDO), a recently proposed meta-heuristic algorithm, can be used to solve any optimization problem. In this paper, a hybrid version of GNDO with Simulated Annealing (SA) called Binary Simulated Normal Distribution Optimizer (BSNDO) is proposed which uses SA as a local search to achieve higher classification accuracy. The proposed method is evaluated on 18 well-known UCI datasets and compared with its predecessor as well as some popular FS methods. Moreover, this method is tested on high dimensional microarray datasets to prove its worth in real-life datasets. On top of that, it is also applied to a COVID-19 dataset for classification purposes. The obtained results prove the usefulness of BSNDO as a FS method. The source code of this work is publicly available at https://github.com/ahmed-shameem/Feature_selection.

7.
Front Psychiatry ; 13: 936052, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35845438

RESUMO

This study examines the impact of G × E interaction effects on non-alcoholic fatty liver disease (NAFLD) among Mexican Americans in the Rio Grande Valley (RGV) of South Texas. We examined potential G × E interaction using variance components models and likelihood-based statistical inference in the phenotypic expression of NAFLD, including hepatic steatosis and hepatic fibrosis (identified using vibration controlled transient elastography and controlled attenuation parameter measured by the FibroScan Device). We screened for depression using the Beck Depression Inventory-II (BDI-II). We identified significant G × E interactions for hepatic fibrosis × BDI-II. These findings provide evidence that genetic factors interact with depression to influence the expression of hepatic fibrosis.

8.
Int J Surg Case Rep ; 96: 107299, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35751966

RESUMO

INTRODUCTION: Mucormycosis is an opportunistic mycosis common in poorly-controlled insulin dependent diabetic patients particularly with ketoacidosis. Fungal osteomyelitis is a life-threatening condition affectation of the nose and paranasal sinuses within the orofacial region. PRESENTATION OF CASE: We present a 63-year-old diabetic male patient with maxillary mucormycotic osteomyelitis threatening his better seeing eye and review the clinical symptoms, relevant imaging, and management. DISCUSSION: We highlight a rare pattern of craniofacial fungal bone infection with maxillary and orbital involvement that ultimately spared the optic nerve. This case report offers the clinician a review of important clinical and diagnostic findings that can help direct the need for orbital exenteration. CONCLUSION: Maxillary mucormycotic osteomyelitis is an aggressive infection that needs to be addressed promptly to prevent fatal consequences.

9.
Bioengineering (Basel) ; 9(1)2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35049720

RESUMO

Male pattern baldness (MPB) is a common condition that has a negative impact on the psycho-social health of many men. This study aims to engineer an alcohol-free formulation to cater for individuals who may have had allergic reactions to alcohol-based preparations. A lipid-based nanoparticle system composed of stearic and oleic acid (solid and liquid lipid) was used to deliver dutasteride (DST) for topical application. Two compositions, with oleic acid (Formulation A) and without (Formulation B), were compared to analyse the role of oleic acid as a potential active ingredient in addition to DST. DST-loaded LNP were prepared using the emulsification-ultrasonication method. All of the prepared formulations were spherical in shape in the nanometric size range (150-300 nm), with entrapment efficiencies of >75%. X-ray diffractograms revealed that DST exists in an amorphous form within the NLP matrices. The drug release behaviour from both LNP preparations displayed slow release of DST. Permeation studies through pig ear skin demonstrated that DST-LNP with oleic acid produced significantly lower permeation into the dermis compared to the formulation without oleic acid. These results suggest that the proposed formulation presents several characteristics which are novel, indicating its suitability for the dermal delivery of anti-androgenic molecules.

10.
Expert Syst Appl ; 193: 116377, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35002099

RESUMO

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It may cause serious ailments in infected individuals and complications may lead to death. X-rays and Computed Tomography (CT) scans can be used for the diagnosis of the disease. In this context, various methods have been proposed for the detection of COVID-19 from radiological images. In this work, we propose an end-to-end framework consisting of deep feature extraction followed by feature selection (FS) for the detection of COVID-19 from CT scan images. For feature extraction, we utilize three deep learning based Convolutional Neural Networks (CNNs). For FS, we use a meta-heuristic optimization algorithm, Harmony Search (HS), combined with a local search method, Adaptive ß -Hill Climbing (A ß HC) for better performance. We evaluate the proposed approach on the SARS-COV-2 CT-Scan Dataset consisting of 2482 CT scan images and an updated version of the previous dataset containing 2926 CT scan images. For comparison, we use a few state-of-the-art optimization algorithms. The best accuracy scores obtained by the present approach are 97.30% and 98.87% respectively on the said datasets, which are better than many of the algorithms used for comparison. The performances are also at par with some recent works which use the same datasets. The codes for the FS algorithms are available at: https://github.com/khalid0007/Metaheuristic-Algorithms.

11.
Saudi Med J ; 42(8): 908-912, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34344816

RESUMO

OBJECTIVES: To measure the effectiveness of tranexamic acid (TXA); in total joint arthroplastyin terms of reducing post-operative blood loss. METHODS: A retrospective cohort study in which patients who had underwent total hip arthroplasty (THA) and TKA between 2010-2018 in a single tertiary center. Those had received TXA (group 1) and those who had received no-TXA (group 2) were evaluated. Unpaired student's t-test was used to compare TXA and no-TXA groups for continuous variables and Chi-square test was used for categorical variables. A p-value<0.05 was considered significant. RESULTS: A total of 385 patients were included, 180 patients received TXA, and 205 patients received no-TXA. Post-operative blood loss was significantly less in TXA group (13.41±9.51, p<0.001). Total drainage output was significantly lower in TXA group compared to no-TXA (373.98±246.12 vs. 487.11±307.13 mL, p<0.001). Blood transfusion units were significantly less in TXA group than in the control group (20 units; 11.1% vs. 50 units; 24.4%, p<0.001). CONCLUSION: Tranexamic acid use in TKA and THA is effective in reducing post-operative blood loss in terms of drop in Hg level, total drainage output and blood transfusion rate.


Assuntos
Antifibrinolíticos , Artroplastia de Quadril , Artroplastia do Joelho , Ácido Tranexâmico , Antifibrinolíticos/uso terapêutico , Perda Sanguínea Cirúrgica/prevenção & controle , Humanos , Estudos Retrospectivos , Ácido Tranexâmico/uso terapêutico
12.
J Orthop Case Rep ; 11(2): 52-56, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34141671

RESUMO

INTRODUCTION: Intraoperative fracture in revision knee arthroplasty is commonly described. Intraoperative fracture during primary total knee arthroplasty (TKA) is a significant yet infrequently reported complication. The literature about intraoperative fractures during primary TKA is limited. It is usually seen in posterior-stabilized prosthesis during primary TKA, however, its occurrence in cruciate-retaining (CR) primary TKA is rarely reported. CASE REPORT: The authors describe a unique case of intraoperative medial femoral condyle fracture in primary CR TKA during bone preparation. The fracture was managed successfully by fixation with a 3.5 mm screw followed by cemented primary CRTKA. Bony union was achieved with a good clinical outcome as shown by the Knee Society Knee Score of 86 and a Function Score of 90 without any signs of prosthesis failure/loosening at 2 years' follow-up. DISCUSSION: Careful pre-operative evaluation and planning are necessary for patients with risk factors to avoid poor outcome. A stable internal fixation abiding the standard principles of fracture fixation and arthroplasty is needed to achieve a satisfactory functional and radiographic outcome, thus avoids early prosthetic failure.

13.
Cureus ; 12(10): e10834, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33173640

RESUMO

Background and objective The predialysis education program (PDEP) is an integral part of the management of patients with end-stage renal disease (ESRD). Hence, the aim of this study was to assess the distribution of renal replacement therapy (RRT) among patients with ESRD who received PDEP counseling at a single tertiary care center in Khamis Mushait, Kingdom of Saudi Arabia (KSA). Methodology In this study, we included 177 patients with ESRD who received a series of structured PDEP counseling sessions between March 2018 and February 2019 at the Armed Forces Hospital, Southern Region, Khamis Mushait, KSA. All patients were offered available RRT options, which included hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), or renal transplantation. Patients' opted RRT modality was recorded and managed as per the international guidelines and institutional protocols. Results Out of 177 patients, 58.8% (104) were males, with a mean age of 59 ± 13.7 years. The most common comorbid condition as the primary diagnosis was diabetic nephropathy in 49.7% (88), followed by hypertension in 30.5% (54), bilateral small kidney in 15.3% (27), and renal stone in 5.1% (nine) of the patients. Among the available RRTs, 51.4% (91) chose HD, 5.1% (nine) decided on CAPD, four patients (2.3%) opted for renal transplantation, while the remaining 41.2% (73) had yet to choose one, out of which 83.6% (61/73) had stage-IV chronic kidney disease (CKD) while the remaining 16.4% (12/73) had stage-V CKD. Conclusions In conclusion, a series of structured PDEP sessions for the patients progressing to ESRD can facilitate their selection of RRT. In a resource-limited setting, such as ours, where the number of patients who seek treatment for ESRD is rising, PDEP can provide patients with adequate information and knowledge to equip them with the ability regarding the selection of a self-care RRT modality.

14.
Pharmaceutics ; 12(10)2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33092119

RESUMO

Dutasteride, licensed as an oral medicine for the treatment of benign prostatic hypoplasia, has been investigated as a treatment for androgenic alopecia. In this study, the potential for dustasteride to be delivered topically in order to reduce systemic exposure, irritation of the skin, and also cytotoxicity was explored. Chitosan oligomer (CSO) was successfully synthesised with lauric acid as a coating for a dutasteride-loaded nanostructured lipid carriers (DST-NLCs) system. DST-NLCs were prepared using a combination of melt-dispersion and ultrasonication. These negatively charged NLCs (-18.0 mV) had a mean particle size of ~184 nm, which was not significantly increased (p > 0.05) when coated with lauric acid-chitosan oligomer (CSO-LA), whilst the surface charge changed to positive (+24.8 mV). The entrapment efficiency of DST-NLCs was 97%, and coated and uncoated preparations were physically stable for up to 180 days at 4-8 °C. The drug release was slower from DST-NLCs coated with CSO-LA than from uncoated NLCs, with no detectable drug permeation through full-thickness pig ear skin from either preparation. Considering the cytotoxicity, the IC50 values for the DST-NLCs, coated and uncoated with CSO-LA were greater than for dutasteride alone (p < 0.05). DST-NLCs and empty NLCs coated with CSO-LA at 25 µM increased the cell proliferation compared to the control, and no skin irritation was observed when the DST-NLC formulations were tested using EpiDerm™. The cell and skin uptake studies of coated and uncoated NLCs incorporating the fluorescent marker Coumarin-6 showed the time-dependent uptake of Coumarin-6. Overall, the findings suggest that DST-NLCs coated with CSO-LA represent a promising formulation strategy for dutasteride delivery for the treatment of androgenic alopecia, with a reduced cytotoxicity compared to that of the drug alone and lower irritancy than an ethanolic solution of dutasteride.

15.
J Diabetes Res ; 2018: 5162162, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30151393

RESUMO

AIM: The purpose of this cross-sectional study was to determine the rates of diabetes device use (insulin pump and continuous glucose monitor (CGM)) and association with glycemic control in youth with type 1 diabetes in a large, diverse pediatric center. METHODS: Demographic and clinical data were obtained from 1992 patients who met the eligibility criteria (age < 26 years, diabetes duration ≥ 1 year, and ≥1 clinic visit in the preceding 12 months). Statistical analyses assessed the likelihood of device use based on demographic characteristics and the association between device use and glycemic control based on most recent hemoglobin A1c (HbA1c). RESULTS: Mean age was 13.8 ± 4.2 years, 50.7% were female, diabetes duration was 6.2 ± 4 years, and mean HbA1c was 8.7 ± 1.8%. Overall, 38.2% of patients were on pump therapy and 18.5% were on CGM. Patients who were non-Hispanic (NH) white, privately insured, and with primary English-speaking parent(s) had higher rates of insulin pump use, as well as CGM use (P < 0.001 for both). Female patients had higher rates of pump use only (P < 0.01). Private health insurance, NH white race/ethnicity, and CGM use were each associated with lower HbA1c (P = 0.03, <0.001, and <0.008, resp.). CONCLUSION: At a large, diverse, pediatric diabetes center, disparities in diabetes device use were present across sex, race/ethnicity, health insurance coverage, and primary language of parent(s). CGM use was associated with lower HbA1c. Quality improvement efforts are underway to ensure improved access, education, and clinical programs for advanced diabetes devices for T1D patients.


Assuntos
Automonitorização da Glicemia/instrumentação , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Adolescente , Adulto , Fatores Etários , Biomarcadores/sangue , Glicemia/metabolismo , Criança , Pré-Escolar , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Valor Preditivo dos Testes , Texas , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Eur J Pharm Biopharm ; 117: 372-384, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28412472

RESUMO

Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair growth. To enhance delivery to the hair follicles and reduce systemic effects, in this study dutasteride has been formulated for topical application, in a nanostructured lipid carrier (NLC) coated with chitosan oligomer-stearic acid (CSO-SA). CSO-SA has been successfully synthesized, as confirmed using 1H NMR and FTIR. Formulation of dutasteride-loaded nanostructured lipid carriers (DST-NLCs) was optimized using a 23 full factorial design. This formulation was coated with different concentrations of stearic acid-chitosan solution. Coating DST-NLCs with 5% SA-CSO increased mean size from 187.6±7.0nm to 220.1±11.9nm, and modified surface charge, with zeta potentials being -18.3±0.9mV and +25.8±1.1mV for uncoated and coated DST-NLCs respectively. Transmission electron microscopy showed all formulations comprised approximately spherical particles. DST-NLCs, coated and uncoated with CSO-SA, exhibited particle size stability over 60days, when stored at 4-8°C. However, NLCs coated with CSO (without conjugation) showed aggregation when stored at 4-8°C after 30days. The measured particle size for all formulations stored at 25°C suggested aggregation, which was greatest for DST-NLCs coated with 10% CSO-SA and 5% CSO. All nanoparticle formulations exhibited rapid release in an in vitro release study, with uncoated NLCs exhibiting the fastest release rate. Using a Franz diffusion cell, no dutasteride permeated through pig ear skin after 48h, such that it was not detected in the receptor chamber for all samples. The amount of dutasteride in the skin was significantly different (p<0.05) for DST-NLCs (6.09±1.09µg/cm2) without coating and those coated with 5% CSO-SA (2.82±0.40µg/cm2), 10% CSO-SA (2.70±0.35µg/cm2) and CSO (2.11±0.64µg/cm2). There was a significant difference (p<0.05) in the cytotoxicity (IC50) between dutasteride alone and in the nanoparticles. DST-NLCs coated and uncoated with CSO-SA increased the maximum non-toxic concentration by 20-fold compared to dutasteride alone. These studies indicate that a stearic acid-chitosan conjugate was successfully prepared, and modified the surface charge of DST-NLCs from negative to positive. These stable, less cytotoxic, positively-charged dutasteride-loaded nanostructured lipid carriers, with stearic acid-chitosan oligomer conjugate, are appropriate for topical delivery and have potential for promotion of hair growth.


Assuntos
Quitosana/química , Sistemas de Liberação de Medicamentos/métodos , Dutasterida/química , Lipídeos/química , Nanoestruturas/química , Ácidos Esteáricos/química , Administração Tópica , Animais , Quitosana/administração & dosagem , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Dutasterida/administração & dosagem , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Humanos , Lipídeos/administração & dosagem , Nanoestruturas/administração & dosagem , Técnicas de Cultura de Órgãos , Pele/efeitos dos fármacos , Pele/metabolismo , Ácidos Esteáricos/administração & dosagem , Suínos
17.
Eur J Pharm Biopharm ; 113: 1-10, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27916704

RESUMO

This study has investigated complexation of fisetin, a natural flavonoid, with three types of cyclodextrins to improve its solubility. Sulfobutylether-ß-cyclodextrin (SBE-ß-CD) showed the highest complexation efficiency while maintaining the in vitro antioxidant activity of fisetin. Addition of 20%v/v ethanol in water improved the amount of solubilized fisetin in the complex 5.9-fold compared to the system containing water alone. Spray drying of fisetin-SBE-ß-CD complex solution in the presence of ethanol produced a dry powder with improved aerosolization properties when delivered from a dry powder inhaler, indicated by a 2-fold increase in the fine particle fraction (FPF) compared to the powder produced from the complex solution containing water alone. The pitted morphological surface of these particles suggested a more hollow internal structure, indicating a lighter and less dense powder. Incorporation of 20%w/w leucine improved the particle size distribution of the powder and further increased the FPF by 2.3-fold. This formulation also showed an EC50 value equivalent to fisetin alone in the A549 cell line. In conclusion, an inhalable dry powder containing fisetin-SBE-ß-CD complex was successfully engineered with an improved aqueous solubility of fisetin. The dry powder may be useful to deliver high amounts of fisetin to the deep lung region for therapeutic purposes.


Assuntos
Antioxidantes/administração & dosagem , Flavonoides/administração & dosagem , Pulmão/metabolismo , beta-Ciclodextrinas/química , Aerossóis , Linhagem Celular Tumoral , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Portadores de Fármacos , Flavonóis , Humanos , Microscopia Eletrônica de Varredura , Difração de Pó , Pós , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria
18.
Eur J Pharm Biopharm ; 88(3): 816-29, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25305582

RESUMO

The potential of amphiphilic chitosan formed by grafting octanoyl chains on the chitosan backbone for pulmonary delivery of levofloxacin has been studied. The success of polymer synthesis was confirmed using FT-IR and NMR, whilst antimicrobial activity was assessed against Pseudomonas aeruginosa. Highly dispersible dry powders for delivery as aerosols were prepared with different amounts of chitosan and octanoyl chitosan to study the effect of hydrophobic modification and varying concentration of polymer on aerosolization of drug. Powders were prepared by spray-drying from an aqueous solution containing levofloxacin and chitosan/amphiphilic octanoyl chitosan. l-leucine was also used to assess its effect on aerosolization. Following spray-drying, the resultant powders were characterized using scanning electron microscopy, laser diffraction, dynamic light scattering, HPLC, differential scanning calorimetry, thermogravimetric analysis and X-ray powder diffraction. The in vitro aerosolization profile was determined using a Next Generation Impactor, whilst in vitro antimicrobial assessment was performed using MIC assay. Microparticles of chitosan have the property of mucoadhesion leading to potential increased residence time in the pulmonary mucus, making it important to test the toxicity of these formulations. In-vitro cytotoxicity evaluation using MTT assay was performed on A549 cell line to determine the toxicity of formulations and hence feasibility of use. The MTT assay confirmed that the polymers and the formulations were non-cytotoxic. Hydrophobically modifying chitosan showed significantly lower MIC (4-fold) than the commercial chitosan against P. aeruginosa. The powders generated were of suitable aerodynamic size for inhalation having a mass median aerodynamic diameter less than 4.5µm for formulations containing octanoyl chitosan. These highly dispersible powders have minimal moisture adsorption and hence an emitted dose of more than 90% and a fine particle fraction (FPF) of 52%. Powders with non-modified chitosan showed lower dispersibility, with an emitted dose of 72% and FPF of 20%, as a result of high moisture adsorption onto the chitosan matrix leading to cohesiveness and subsequently decreased dispersibility.


Assuntos
Engenharia Química/métodos , Quitosana/síntese química , Interações Hidrofóbicas e Hidrofílicas , Levofloxacino/síntese química , Microesferas , Administração por Inalação , Quitosana/administração & dosagem , Quitosana/metabolismo , Levofloxacino/administração & dosagem , Levofloxacino/metabolismo , Tamanho da Partícula , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Difração de Raios X
19.
J Family Community Med ; 15(1): 43-50, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23012166

RESUMO

BACKGROUND: Death certification is a vital source of information used in mortality statistics worldwide to assess the health of the general population. This study focuses on the consistency of information between the death reports and the clinical records (files) of deceased patients in two hospitals: the King Khalid University Hospital (KKUH) and King Fahad National Guard hospital (KFNGH) in Saudi Arabia. METHODS: A random sample of the records of 157 deceased patients' registered in 2002 in the two hospitals was retrospectively reviewed independently to determine the underlying cause of death and compare them with death reports. It was also to check the accuracy of the translation from English in to Arabic. RESULTS: It was found that the underlying cause of death was misdiagnosed in 80.3% of the death reports. When the two hospitals were compared, no significant difference was observed (p>0.05). In addition, 81.8% of the accurate (correct) death reports in both hospitals were of patients who had died of a malignant disease. However, the translation of the underlying cause of death in KFNGH was correct in 86.1% of the death reports, while in KKUH it was only 25%, which is highly statistically significant (p<0.0001). CONCLUSION: With the limitation of studying only a small number of cases, these results indicate a discrepancy between the file and death reports in relation to the cause of death. Also, the translation of the cause of death was inconsistent in the two hospitals. Hence, there is a real need to adopt suitable measures to improve the quality of death certification.

20.
Pak J Pharm Sci ; 18(1): 1-5, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16431376

RESUMO

Topical emulsions stabilized with non-ionic emulsifiers have been an attractive alternative as vehicles for drug delivery, particularly for the patients suffering from dermatological problems. Haruan (a natural wound healer) creams were formulated with different types of emulsifiers (Tween 80 and Span 80) using different grades of Malaysian Palm-oleins (DFPL 56, 60, 62 and 65). The stability (at room temperature and accelerated stability testing) of the various creams was evaluated at different temperatures (5, 25 and 45 degrees C) for a period of 6 months by measuring changes in droplet size, viscosity and percentage oil separation. The emulsifier type and concentration showed pronounced effect on the physicochemical properties of the cream, whereas storage time did not. This study suggested that the choice of emulsifiers and concentration of haruan extract are the most important factors in the stability of the haruan creams.


Assuntos
Fármacos Dermatológicos/química , Perciformes/metabolismo , Óleos de Plantas/química , Extratos de Tecidos/química , Animais , Composição de Medicamentos , Estabilidade de Medicamentos , Emulsões , Pomadas , Óleo de Palmeira , Tamanho da Partícula , Reologia , Extratos de Tecidos/isolamento & purificação
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